1. Activity of rat hepatic microsomal and peroxisomal long-chain (palmitoyl) and nafenopin-CoA ligases were studied following administration of either clofibric acid, di-(2-ethylhexyl)phthalate (DEHP) or phenobarbitone. 2. Clofibric acid significantly induced the peroxisomal palmitoyl and nafenopin-CoA ligases, whilst no induction of the equivalent enzymes was observed in the microsomal fraction. 3. DEHP induced only palmitoyl-CoA formation in peroxisomes, whilst all enzymes were refractory to phenobarbitone treatment. 4. The enzyme-specific patterns of induction both intra- and inter-organelle suggest that the palmitoyl and nafenopin-CoA ligases are under different regulatory control. 5. Modulation of both the rate and extent of nafenopin-and palmitoyl-CoA formation was both agent and organelle specific. 6. This study highlights the difficulty in delineating the individual roles of both fatty acyl-CoAs and xenobiotic-CoAs in peroxisome proliferation.