The effects of meals and meal composition on the bioavailability of fenretinide, N‐(4‐hydroxyphenyl) retinamide, a synthetic retinoid undergoing clinical trials, were examined in two separate studies using an open, randomized, crossover design. In the first study, 13 healthy male volunteers received 300‐mg doses of fenretinide (1) while fasting and (2) after a high‐fat breakfast. In a subsequent study, 15 subjects received 300 mg fenretinide after each of three different test meals (high‐fat, high‐protein, and high‐carbohydrate) separated by a 1‐week washout period. Plasma specimens obtained over a 72‐hour period after each treatment were assayed by high‐pressure liquid chromatography to characterize the effects of a meal and meal composition on the bioavailability of fenretinide. Results from the initial study demonstrated a significant increase in the bioavailability of fenretinide after a high‐fat meal. In the follow‐up study, the bioavailability of fenretinide, as assessed by total area under the plasma concentration curve, was three times greater after the high‐fat meal than after the high‐carbohydrate meal. This supported the findings of the first study. Although to a lesser extent, the high‐protein meal also produced a greater area under the curve than the high‐carbohydrate meal. These combined findings demonstrate that the bioavailability of fenretinide is markedly influenced not only by administration with meals but also by the specific composition of such meals.