Using the Princeton School Family Study, our specific aim was to estimate the prevalence of familial hyper- and hypouricemia, to estimate the proportion of probands' first-degree relatives who were similarly affected, and to evaluate the contribution of diseases, drugs, and alcohol intake (if any) to uric acid levels. We studied 379 probands and a total of 1928 subjects, 125 and 52 black probands from a randomly recalled group, 147 white and 55 black probands from a hyperlipidemic recall (top decile cholesterol and/or triglyceride) group. Familial hyper- and hypouricemias were arbitrarily identified in those kindreds having at least two first-degree relatives in the same decile as the proband, top or bottom respectively, for serum uric acid. No probands had symptomatic gout. Diseases, drugs, and alcohol intake were not consistently associated with aggregations of high and/or low uric acid levels in families, and had little relationship to uric acid levels in individuals. Of the 177 randomly recalled probands, and of the 55 black probands in hyperlipidemic recall group, none had familial hyperuricemia. Of the 147 white hyperlipidemic recall group probands and their kindreds, 2 had familial hyperuricemia, with concurrent primary hyperlipoproteinemia and hypertension. Familial hypouricemia was present in 1 of 125 white and in 1 of 52 randomly recalled black kindreds, and in 3 of 147 white and 3 of 55 hyperlipidemic recall black kindreds. While familial clustering of hyperuricemia was limited, clustering of hypouricemia was much more marked. Seventy-four and 84% respectively of first-degree relatives of hypouricemic white and black probands had uric acid < the 50th percentile. In randomly recalled probands and their first-degree relatives there were significant inverse partial correlations between uric acid and high density lipoprotein cholesterol. Inverse associations of uric acid with high density lipoprotein cholesterol and the concurrence of hyperlipoproteinemia and hypertension in hyperuricemic families points to the importance of lipoprotein and blood pressure screening in families with asymptomatic hyperuricemia. The potential ramifications of within-family clustering of hypouricemia need to be further assessed in populations, particularly in regards to uric acid nephrolithiasis.