The role of HL-A matching in the clinical outcome of 159 consecutive first cadaver renal allografts at the Johannesburg General Hospital has been analysed over a 7-year period, April 1968-May 1975. Over-all actuarial graft survival was 69% at 1 year and 57% at 7 years. When all cases were considered together there was a trend towards improved graft survival with better grades of matching, but this was not statistically significant. Presensitisation had an adverse effect on graft survival. Donor-recipient combinations with no demonstrable FOUR locus mismatches provided a significantly superior graft survival rate of 82% 1-6 years after transplantation. The majority of these compatible for HL-A 7, 8 OR 12, and therefore may have been matched indirectly for lymphocyte activating determinants. Relatively inferior graft survival was observed with FOUR locus incompatibility in patients who had been presensitised, and when donor-recipient combinations had no serologically determined antigens in common, particularly in the donor "full house" situation. Despite these unfavourable immunogenetic circumstances, approximately 50% of grafts functioned well for long periods, and not infrequently clinical considerations took precedence over immunological considerations in the selection of recipients. This policy is justified by over-all results, the critical shortage of cadaver organs in relation to clinical requirements and the rare occurrence of combinations with superior HL-A matching. Specific allograft tolerance remains the goal of clinical organ transplantation.