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Amoraim discuss the machlokes between Rebbe Meir and Rebbe Shimon if נותן טעם לפגם prohibits a mixture. Ulla says: מחלוקת שהשביח ולבסוף פגם – the dispute is only where [the forbidden flavor] first improved the mixture and only eventually harmed it. Because it initially improved the mixture’s flavor, Rebbe Meir says the mixture becomes forbidden. אבל פגם מעיקרא דברי הכל מותר – But where it harmed the mixture’s flavor from the beginning, all agree the mixture is permitted. Rebbe Yochanan says: בפוגם מעיקרא מחלוקת – the dispute pertains to where [the forbidden flavor] harmed the mixture’s flavor from the beginning. The Gemara asks if Rebbe Yochanan meant that all agree that השביח ולבסוף פגם is forbidden, or that they argue in both cases. Proof is eventually brought from a Baraisa discussing leaven of terumah and leaven of chullin which fell into a dough, which first leavened it and then overleavened and ruined it. The סיפא states that if the terumah fell in first, all agree it is prohibited (since it first improved the dough). This proves their machlokes is only by פגם מעיקרא.
The above Baraisa taught that if terumah leaven and chullin leaven fell simultaneously into a dough, and first leavened it and then ruined it, the Rabbonon prohibit the dough, because the prohibited leaven caused the dough to be leavened faster than it would have with only the chullin leaven. Rebbe Shimon permits the dough, because although it was first improved, the permitted and prohibited leavens improved it together. The Gemara asks, according to Rebbe Shimon, the permitted and prohibited leavens should combine to prohibit the dough (since the prohibited leaven contributed to its initial improvement)!? It answers that Rebbe Shimon is following his view that אפי' איסור ואיסור נמי לא מיצטרפי – even one prohibition and another prohibition do not combine to prohibit a mixture. In a Mishnah, the Tanna Kamma says that ערלה and כלאי הכרם (both of which prohibit at a ratio of up to one in two hundred) combine to prohibit a mixture, but Rebbe Shimon says they do not combine to prohibit it, and each element is nullified.
The Gemara relates an incident in which a mouse fell into a barrel of beer, and the beer absorbed its flavor. Rav prohibited the beer in consumption, and Rav Sheishess was asked if Rav holds נותן טעם לפגם is אסור. He responded that ordinarily, Rav holds נותן טעם לפגם is permitted. והכא חידוש הוא – But here, [the prohibition against eating a mouse] is a novelty, דהא מימאס מאיס ובדילי אינשי מיניה – because it is repulsive, and people stay away from eating it on their own, ואפילו הכי אסריה רחמנא – and even so, Hashem prohibited it. Since the Torah did not need to prevent people from eating it, the prohibition teaches that it prohibits a mixture even though it is נותן טעם לפגם. Rava says the halachah is that נותן טעם לפגם is always מותר, even in the case of repulsive שרצים. Therefore, he said he was unsure if Rav’s stringent ruling in the case of the mouse in the beer was because he holds נותן טעם לפגם is אסור (in which case we do not pasken like him), or that he holds the mouse improves the beer’s flavor, and the halachah could follow him.
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