Microliter quantities of a Prudhoe Bay crude oil (PBCO) applied to the shell of fertile chick eggs during various stages of development induced cytochrome P-450 levels and mixed-function oxidase activities within the liver of the embryo. PBCO (5 microliter) applied on Day 11 of incubation was found to maximally induce within 24 hr embryo hepatic cytochrome P-450 levels (fourfold), naphthalene hydroxylase (sixfold), benzo[a]pyrene 3-hydroxylase (14-fold), and 7-ethoxyresorufin O-deethylase (24-fold). Glutathione S-transferase was not induced. Crude oils are known to be highly toxic to avian embryos, especially during the early stages of development. The LD50 of PBCO and Hibernia crude oil applied to the egg shell on Day 8 of incubation was found to be 1.3 and 2.2 microliter, respectively. Mixed-function oxidase-dependent metabolism of crude oil components may be required for toxicity since administration of 20 micrograms of disulfiram in dioxane 1 hr prior to application of 1.3 microliter of PBCO reduced embryo mortality from 60 to 20%.