Several genes contribute to the development of calcium oxalate nephrolithiasis as it is a polygenic disease. To explore the influence of genetic factors on oxalate excretion we have examined the distribution of oxalate excretions in 101 normal individuals who consumed self-selected diets. The distribution was apparently trimodal, consistent with the existence of three classes of oxalate excretors reflecting two allelic genes determining high and low oxalate excretion occurring with frequencies of 0.32 and 0.68 respectively. The pattern of inheritance in eight families was compatible with the expression of a pair of codominant alleles. A comparison of the distribution of excretory classes among the 101 normal individuals with that of 101 calcium oxalate stone formers suggests that high oxalate excretion may be associated with a 4-fold increased risk of stone disease and intermediate excretion with a 1.6-fold increase. Control of dietary factors influencing oxalate excretion apparently improved the discrimination between excretory classes in 17 individuals but the intra-individual variability in oxalate excretion was not reduced in four of nine individuals in whom this parameter was evaluated. More stringent dietary control than that applied in this study may be required before more extensive genotyping of individuals is attempted.