Roxatidine is an H(2) receptor blocker frequently used in the treatment of peptic ulcers. H(2) receptor blockers are reported to show antifertility activity. To examine the mechanism of antifertility, estrogenic and antiestrogenic activity was studied using an in vitro rat and rabbit uterine receptor binding assay and in vivo using the uterotrophic assay in immature Wistar rats. The results revealed that roxatidine showed mild receptor binding affinity to both rat and rabbit uterine receptors when compared to estradiol. Interstingly, in vivo roxatidine increases the wet uterine weight of immature Wistar rats significantly (P<0.001) when compared to a control group. The increase in uterine weight within the roxatidine treated group was somewhat similar to that of the estradiol treated group. Histopathological results and the structure of the roxatidine support that H(2) receptor blocker roxatidine is an estrogenic compound.