The objective of this study was to investigate the effect of dietary zinc on endogenous production of free radicals in lung and liver microsomes. Male weanling rats were fed a zinc-deficient basal diet containing less than 1.1 ppm zinc, or were pair-fed or fed ad libitum a zinc-adequate diet supplemented with 100 ppm zinc. The isolated microsomes (100,000 X g precipitate) of lung and liver were incubated with 0.1 M PBN (spin trap) and 0.3 mM NADPH (cofactor) at 37 degrees C for 1.0 h. A carbon-centered free radical (aN = 16.0 G, aH beta = 3.4 G) was trapped in both lung and liver microsomes. There was a significant increase in the concentration of carbon-centered free radicals generated in lung microsomes in animals fed a zinc-deficient diet. Dietary zinc status did not significantly affect the concentration of free radicals in liver microsomes. The amount of free radicals generated is proportional to microsomal protein concentration and is linear with protein concentration between 5 and 20 mg per milliliter of incubate. The free radicals formed in the microsomal system were dependent on the presence of NADPH. Carbon monoxide inhibited 40-50% of the free radical production in both lung and liver microsomes. The results suggest that dietary zinc deficiency stimulates the production of endogenous free radicals in rat lung microsomes by an NADPH- and cytochrome P-450-dependent system.