Contrary to an earlier opinion that nicotine has no effect on the fertility of male animals or humans, the present experimental study using male inbred Fisher rats demonstrates that the reproductive capacity of the animals is greatly reduced when injected with nicotine, and that the effect is much greater in male than in female Fisher rats similarly injected with nicotine. This is in accord with some earlier histological and morphological studies which have shown that female rodents have a greater tolerance to nicotine than their male counterparts. It is also confirmed by the cytologic observations of the present study. These observations show that, similar to female rats, inflammatory processes, as evidenced by an increased number of lymphocytes and/or polymorphonuclear leukocytes, are responsible for the decrease in fertility. However, the cytological profile is profoundly different in the two sexes: virulent inflammatory conditions begin much earlier in male rats, they are more frequent and, whereas the condition is reversible in the female animal when nicotine treatment is discontinued, it is not in some male rats, and inflammatory conditions persist for the entire life as does infertility. However, the life span of nicotine-treated male rats is greater than in female nicotine-treated rats, although it is shorter in both sexes than in their respective controls; in some male nicotine-treated rats, the life span is greater not only than in their male controls but even than in their female counterparts. Possible explanations for this apparently paradoxical life-prolonging effect of nicotine treatment are reviewed, but the evidence is either conflicting or insufficiently established and requires further study.