To determine the nature and prevalence of spondyloarthropathy (SpA) among the 1st degree relatives of probands with either Reiter's syndrome (RS) or ankylosing spondylitis (AS), 599 relatives of 223 consecutive probands (110 RS and 113 AS) were blindly evaluated in a controlled study. Analysis was by questionnaire, radiographic examination without knowledge of proband or relative status and, where relevant, by chart review. No cases of RS were found among the 277 relatives of probands with AS. In contrast, 11 of 322 relatives of probands with RS did have RS which was neither temporally related in onset nor due to a common epidemic source (p less than 0.01). There were 18 cases of AS among the relatives of the probands with AS compared to only 7 cases among the relatives of the patients with RS (p less than 0.05). Two probands with AS each had 2 relatives with AS. Thus, the degree of familial aggregation in RS (11/110; 10%) approaches that seen in AS (16/113; 14%) and the 2 diseases tend to breed true within families. These data suggest that there may be different genetic backgrounds in patients with RS and AS, despite the fact that both conditions are typically associated with HLA-B27.