The effects of several endogenous substances on the oxidative degradation of unsaturated lipids (lipid peroxidation) in the adrenal and liver in-vitro were compared. Adrenal and hepatic microsomes were isolated from male English-Short-Hair-guinea-pigs, and effects of NADPH, ferrous ion (Fe+2), ferric ion (Fe+3), and L- ascorbate on lipid peroxidation were evaluated. Lipid peroxidation was measured by malonaldehyde (MDA) production, as detected by the thiobarbituric-acid test. Fe+2 caused a concentration dependent increase in lipid peroxidation by adrenal microsomes between 10(-6) and 10(-3) molar (M). Fe+3 was much less effective in adrenals, while these ions had similar activities in liver microsomes. Ascorbate at 10(-4)M interacted synergistically with Fe+2 at low but not high concentrations to increase lipid peroxidation in adrenal microsomes. Ascorbate acted synergistically with Fe+3 at all concentrations. Higher concentrations of ascorbate reduced lipid peroxidation, possibly due to manifestation of its antioxidant properties. These effects were seen in heat treated microsomes as well, indicating the nonenzymatic nature of the inhibited activity. NADPH alone had no effect on adrenal microsomes but showed a dose dependent stimulation of enzymatic peroxidation in the presence of low levels of Fe+2 and, to some extent, Fe+3. At higher iron concentrations, NADPH inhibited nonenzymatic lipid peroxidation. The capacity for nonenzymatic lipid peroxidation was greater in adrenal versus hepatic microsomes. Enzymatic lipid peroxidation was stimulated by NADPH in the absence of Fe+2 for hepatic, but not adrenal microsomes. The authors conclude that multiple interactions between a variety of substances can have profound effects on lipid peroxidation in adrenals, and that liver and adrenal lipid peroxidation processes are controlled differently.