Thirty-two patients who fulfilled criteria for subacute cutaneous lupus erythematosus (SCLE) were examined for their immunogenetic associations. Our results confirm the previously reported association of HLA-DR3 (15/31 48% P less than 0.01) and also demonstrate an increase in HLA-DR2 (14/31, 45%, P = less than 0.05). These findings indicate there are two distinct immunogenetic (HLA) populations of Ro(SS-A) antibody-positive SCLE patients. The increased frequency of HLA-DR2 and DR3 appears to be associated with expression of the Ro(SS-A) antibody, since no HLA associations were seen in Ro(SS-A)-negative SCLE patients when compared with normal population controls. Furthermore, these data indicate that the distinctive cutaneous lesions of SCLE are not associated with one specific HLA allele, as previously suspected. These findings contrast with the relatively homogeneous immunogenetic background seen in other lupus erythematosus subsets with a high frequency of Ro(SS-A) antibody, i.e., neonatal lupus erythematosus and Sjögren's syndrome/lupus erythematosus overlap (increased frequency of HLA-DR3, DQw2 and DRW52).