Probucol markedly reduces the LDL-C level in hyperlipidemic patients. However, it also reduces HDL-C which is believed to result in an anti-atherosclerotic effect. Many hyperlipidemic patients treated with Probucol show a marked reduction in the HDL-C level, and administration of the agent to these patients requires proper caution. In this study, factors useful for predicting the reduction in HDL-C were examined in order to be able to predict the problem before actual administration. Probucol (250-750 mg/day) was administered to 30 patients with type II hypercholesterolemia. Among them, 23 patients showed a decrease greater than 20% in the HDL-C level after administration. To evaluate the factors which permit identification of this group, linear descriminant function analysis was performed using 12 pre-administration lipid levels. The analysis indicated that the Apo A-I/HDL-C ratio before Probucol has the greatest predictive value (F = 17.8, P less than 0.01) of all the parameters, and that the HDL-C level is reduced by 20% or more by Probucol administration when this ratio is 5.3 or less.