We have investigated androgen-binding properties of the androgen receptor (AR) in cultured suprapubic skin fibroblasts from six subjects with Kennedy's disease (X-linked spinal and bulbar muscular atrophy). Binding of the synthetic androgen methyltrienolone (R1881) was measured in a monolayer assay, and Scatchard analysis was performed to determine the total number of binding sites and the apparent binding affinity (Kd) of the AR for androgen. Five of the six subjects investigated had an abnormal apparent binding affinity, with Kd values ranging from 0.34-11.7 nmol/L, more than 2 SD from the mean of the normal range (0.19 +/- 0.06 nmol/L). In this group of six patients, there was a significant correlation between the AR Kd and the severity of testicular atrophy and gynecomastia. The number of CAG repeats in the expanded region of exon A of the AR gene was determined in all subjects from whom suprapubic skin fibroblasts were cultured and an additional 12 subjects with Kennedy's disease. In the total group of 18 subjects investigated, there was a trend for an increasing number of CAG repeats associated with decreasing age at onset of different symptoms; however, this correlation was not statistically significant. Thus, we report for the first time a quantitative abnormality of the AR apparent binding affinity in subjects with Kennedy's disease, which appears to be related to the severity of the symptoms of androgen insensitivity.