The Trp64Arg mutation of the beta3-adrenergic receptor (beta3-AR) has been linked to earlier onset of non-insulin-dependent diabetes mellitus (NIDDM), insulin resistance, abdominal obesity, and an increased capacity to gain weight in some European and Japanese populations. We studied the prevalence of the mutation and its association with NIDDM and obesity in our population, in which both rates are high, especially in women. The frequency of the homozygous mutation was 1.53%, and of the Arg allele, 10.5%. Rates were similar in men and women. Significantly higher body mass index (BMI), weight, hip circumference, and fasting and postchallenge 2-hour blood glucose concentrations were associated with the presence of the Arg allele in women but not in men. The association with weight and hip measurements and with hyperglycemia was present only in women aged less than 55 years. In multivariate analysis, the mutation was associated with the BMI and sex in a model that also included age. The variation in fasting and 2-hour blood glucose levels was predicted by beta3-AR, gender, age, and BMI. These results suggest that the presence of the mutation contributes to obesity and hyperglycemia in our female population.