Benzo[a]pyrene (BP; 50 mg/kg) or methadone (5 mg/kg) was given subcutaneously to pregnant rats at different stages of gestation. Both BP and methadone affected the reproductive performance of pregnant rats by significantly increasing the number of resorptions and fetal wastage, and by decreasing the fetal weight. The same dosage levels of BP and methadone were also given to pseudopregnant rats (PSP) with an induced decidual cell reaction (DCR) in an attempt to distinguish whether adverse effects occur in the maternal or fetal compartment or both. Since the hormonal requirements for DCR and implantation are similar and the anatomical, histological, cytological, time sequential changes as well as appearance of the vasculature system for DCR and decidua are indistinguishable, PSP with DCR is similar to pregnancy except for the lack of a fetal compartment. BP, in this PSP model, significantly reduced the uterine wet weight and cyclic nucleotide (cAMP) and cGMP) levels whereas methadone was without a detectable effect. Our findings then suggest that BP may exert its effects adversely on both the maternal and fetal compartments, whereas methadone may act primarily in the fetal compartment.