A total of 167 patients undergoing investigation for suspected coronary artery disease (CAD) were genotyped for restriction fragment length polymorphisms (RFLP) at the apo A-1/C-III locus and the insulin gene locus using cloned human apo A-1 and insulin gene probes. The study group was subdivided into patients with absent or minimal CAD, intermediate CAD and severe obstructive CAD. An Sst-1 polymorphism located in the 3' non-coding region of the apo C-III gene identifies two alleles. One of the alleles (S2) showed a significantly increased frequency in the subjects with severe obstructive CAD (18%) compared with patients with minimal or absent CAD (6%) (P less than 0.025) and normolipidaemic control subjects. This A-1/C-III polymorphism may be a marker for an abnormality in the A-1/C-III genes predisposing to atherosclerosis. In contrast to a previous report, we found no increase in the frequency of the Class 3 insulin alleles in subjects with severe CAD.