We have studied liver biopsies obtained in 12 hyperlipoproteinemic (HLP) patients (type II, 6; type IV, 6) treated with diet and fenofibrate, and in 15 patients (type II, 11; type IV, 4) receiving diet only. Electron microscopy of liver biopsies and the morphometric analysis according to the method of Weibel and Rohr showed mitrochondrial changes in patients treated with fenofibrate, these changes depending on the type of hyperlipoproteinemia. In type II HLP, we found a decreased volume of normal mitochondria (fenofibrate, 125.72 +/- 17.04 X 10(-3) cm3/cm3; diet only, 185.84 +/- 8.96 10(-3), P less than .05). In type IV HLP we found a decreased number of giant mitochondria (fenofibrate, 0.08 +/- 0.03 X 10(10) cm-3; diet only, 0.32 +/- 0.08 X 10(10) cm-3, P less than .05) and a decreased volume of altered mitochondria (fenofibrate, 6.00 +/- 1.44 X 10(-3) cm3/cm3; diet only, 13.61 +/- 1.17 X 10(-3), P less than .05). In contrast with the rodent studies, the present study shows no change in the number of volume of peroxisomes.