Barbiturates and miscellaneous drugs, including organochlorine pesticides, are believed to bring about a generalized nonspecific induction of microsomal enzymes through similar mechanisms. However, previous work indicates that the metabolism of toxicant may be selectively altered by pretreatment with different pesticides and drugs. This study compares the effect of pretreatment with one of eight organochlorine pesticides on the metabolism of lindane and on the activity of various hepatic microsomal enzymes in the rat. Forty-eight weanling, female rats were randomly assigned to 1 of 8 treatment groups and received daily oral injections of 1 mg of either chlordane, DDT, hexachlorobenzene, Mirex, Penphene, Pentac, Toxaphene, or just peanut oil. On the eighth day all animals received 1.7 mg of lindane (containing 1.49 uCi of [14C]lindane) in place of their previous treatment and they were sacrificed at 24 hr later. In general, DDT, Mirex, chlordane and hexachlorobenzene appear to be the most effective inducing agents followed by toxaphene, Pentac and Penphene. However, while the in vitro activity of various microsomal enzymes was increased to the greatest extent by pretreatment with Mirex, the metabolism of lindane was significantly highest in the animals receiving DDT. DDT and hexachlorobenzene pretreatment resulted in the excretion of more free chlorophenols and neutral metabolites, while Mirex and chlordane stimulated the excretion of more conjugated chlorphenols and highly polar metabolites. DDT was unique in stimulating the excretion of the metabolite 2,3,4,5-tetrachlorophenol. The results of this study indicate the possibility of rather selective enzyme responses to certain organochlorine pesticides and suggest that these compounds may induce microsomal enzymes through dissimilar mechanisms.