The influence of HLA A, B, DR on the incidence and symptoms of cytomegalovirus (CMV) infection was investigated in 143 patients who, between October 1st, 1987 and December 31st, 1989, received kidneys from cadaveric donors. Systematic virological monitoring was carried out weekly during the first hospitalization and thereafter at each new hospitalization or in the presence of clinical signs suggestive of viral infection. The diagnosis of CMV was based on positive isolation in blood or urine, or seroconversion, or 4-dilution rise in the anti-CMV antibodies titre. HLA grouping of all recipients was made in the same histocompatibility laboratory. Immunosuppression was obtained with a quadruple therapy consisting of corticosteroids (15 mg/kg before transplantation, then 1 mg/kg for 10 days, then gradually tapering off dosage), azathioprine (2 to 3 mg/day), cyclosporin A (2 mg/kg i.v. followed by an oral dose adjusted to the residual levels) and a randomized treatment with either monoclonal anti-CD3 antibody or anti-thymocyte globulins administered during the first 10 days. The incidence of CMV infection was 56 percent (80/143), with 25 percent of primary infection (20/80). The number of DR compatibilities was found to have a significant influence on the incidence of CMV infection, which rose from 22 to 50 and 65 percent respectively in the group of patients with 2.1 or 0 DR compatibility (P less than 0.02). The degree of B + DR compatibility was also associated with the occurrence of CMV infection, the incidence of which rose from 0 to 36, 59, 43.5 and 71 percent respectively in the group of patients with 4, 3, 2, 1, 0 B + DR compatibility (P less than 0.03). The incidence of primary CMV infection increased with the number of DR incompatibilities, rising from 0 to 29 and 52 percent respectively in the group of patients with 0, 1 or 2 DR incompatibilities. The symptoms and severity of CMV infection were significantly influenced by the degree of DR and B + DR compatibility. Despite a very strong association between graft rejection and CMV infection (P less than 0.000001), no influence of HLA, and particularly DR or B + DR compatibility on the incidence and number of graft rejections could be demonstrated. It is concluded that, under the above-described quadruple therapy, the HLA DR and B + DR compatibility exerts a predominant influence on the occurrence and severity of CMV infection, and that this effect is independent of any action on graft rejection.(ABSTRACT TRUNCATED AT 400 WORDS)