Using controlled in vivo and in vitro pharmacological methods, we evaluated the safety of papaya (Carica papaya) consumption in pregnancy with reference to its common avoidance during pregnancy in some parts of Asia. Ripe papaya (Carica papaya L. (Caricaecae) blend (500 ml/l water) was freely given to four groups of Sprague-Dawley rats at different stages of gestation (days 1-5, 6-11, 12-17 and 1-20). The control group received water. The effect of ripe papaya juice and crude papaya latex on pregnant and non-pregnant rats' uteri was also evaluated using standard isolated-organ-bath methods. The daily volumes (ml) of ripe papaya blend consumed by the treated group were significantly (P<0.05) more than water consumed by the control (control 40.3 (sd 11.6) v. treated 64 (sd 19.0)). There was no significant difference in the number of implantation sites and viable fetuses in the rats given ripe papaya relative to the control. No sign of fetal or maternal toxicity was observed in all the groups. In the in vitro study, ripe papaya juice (0.1-0.8 ml) did not show any significant contractile effect on uterine smooth muscles isolated from pregnant and non-pregnant rats; conversely, crude papaya latex (0.1-3.2 mg/ml) induced spasmodic contraction of the uterine muscles similar to oxytocin (1-64 mU/ml) and prostaglandin F(2 alpha) (0.028-1.81 microm). The response of the isolated rat uterine smooth muscles to 0.2 mg crude papaya latex/ml was comparable to 0.23 microm prostaglandin F(2 alpha) and 32 mU oxytocin/ml. In the 18-19 d pregnant rat uterus, the contractile effect of crude papaya latex was characterized by tetanic spasms. The results of the present study suggest that normal consumption of ripe papaya during pregnancy may not pose any significant danger. However, the unripe or semi-ripe papaya (which contains high concentration of the latex that produces marked uterine contractions) could be unsafe in pregnancy. Though evaluation of potentially toxic agents often relies on animal experimental results to predict risk in man, further studies will be necessary to ascertain the ultimate risk of unripe papaya-semi-ripe papaya consumption during pregnancy in man.