Interactions of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and estradiol were studied in three strains of mice: CD-1 and C57B/6 (TCDD sensitive) and DBA/2 (TCDD resistant at lower doses). Immature females were injected with 0-200 ng/kg/day estradiol for 2 weeks, s.c. On days 7, 9, 11, and 13, mice received 10 micrograms TCDD/kg by gavage. Relative uterine weight increased in mice of all three strains treated with estradiol alone. Uterine imbibition was suppressed by TCDD treatment, although this effect was antagonized in a saturable manner by coadministration of estradiol. TCDD induced aryl hydrocarbon hydroxylase (AHH) in liver microsomes of treated mice independent of estradiol dose and strain of mice (the dose of TCDD used was high enough to cause AHH induction in the resistant DBA/2 mice). Treatment of CD-1 mice, but not other strains, with TCDD and estradiol resulted in a decrease in the electrophoretic band of hepatic microsomal proteins comigrating with cytochrome P-450a and epoxide hydrase.