To study demographic, anthropometric and metabolic determinants of weight change, we divided a random sample of 1493 Mexican Americans and non-Hispanic whites into two groups: weight gainers and weight losers. This classification was based on the weight change during the eight-year follow-up of participants of the San Antonio Heart Study, a population-based longitudinal study of diabetes and cardiovascular disease. Men gained significantly less weight and lost more weight than women. The average gains for weight gainers were 6.1 kg and 6.8 kg for men and women respectively; and the average losses for weight losers were 4.4 and 3.4 kg for men and women respectively. There was no ethnic difference in either category of weight change. Weight gainers were significantly younger and leaner than weight losers. Fasting insulin was the only independent metabolic predictor of weight change and only among the most obese tertile of the population: the higher the baseline levels of fasting insulin, the less the likelihood of gaining and the greater the likelihood of losing weight. Our results support the hypothesis that insulin resistance is part of a negative feedback mechanism that attenuates further weight gain among the obese.