Lead is a widely spread environmental pollutant known to affect both male and female reproductive systems in humans and experimental animals. The present study investigated the effect of ( ) an acute exposure to lead 75 mg lead per gram of body weight 1 or 24 h before hormone treatment on different parameters of estrogen stimulation in the rat uterus. Lead pretreatment enhanced some parameters of estrogen stimulation and inhibited other estrogenic responses, and the remaining parameters were unaltered. The interaction with responses to estrogen was different depending on whether lead pretreatment was 1 or 24 h before hormone stimulation. The estrogenic responses mostly affected were uterine eosinophilia, endometrial edema, uterine luminal epithelial hypertrophy, and mitosis in various-but not all-uterine cell types. In some cell types, estrogen-induced mitotic response developed earlier under the effect of lead exposure. Results revealed an interaction with the different mechanisms of estrogen action in the uterus at various levels, that some cell types are more sensitive to lead than others, and that the effect of exposure changed with time after lead pretreatment. The relevance of the results are discussed in relation to lead-induced infertility, mutagenicity, and carcinogenicity; possible mechanisms of action are proposed.