The influence of the crude aqueous extract of Carica papaya L. (Caricaceae) seeds has been studied on semen profile, fertility, body and organ weight response, and toxicology in male albino rats. The extract was administered at the dose regimens of 10 and 50 mg/animal/day orally for 30, 60, and 90 days and 0.1 and 1.0 mg/animal/day intramuscularly for 15 and 30 days. Cauda epididymal sperm motility and count was reduced significantly at low and high dose regimens both in the oral as well as the intramuscular groups. The reduced sperm motility was associated with morphological defects. Testicular sperm counts were also reduced in all the treatment groups except the low dose intramuscular group. Fertility tests showed dose- and duration-dependent reduction and zero fertility was observed at high dose regimens of the oral and intramuscular groups following 60 and 30 days of treatment, respectively. Testicular weight was reduced in all the treatment groups, whereas accessory sex organs showed a variable response. Body weight and toxicological observations did not show any untoward response. Fertility and all other associated changes returned to normal within 45 and 30 days of treatment cessation in the oral and intramuscular groups, respectively. The data revealed that reversible sterility could be induced in male rats by papaya seeds aqueous extract treatment without adverse effects on libido and toxicological profile.