The effect of duration of obesity on incidence of non-insulin-dependent diabetes mellitus (NIDDM) was determined among Pima Indians. Duration of obesity was defined as the time since body mass index (BMI) was first known to be at least 30 kg/m2. Among 1057 participants eligible for study, there were 224 incident cases of NIDDM in 5975 person-yr of follow-up. The association of duration of obesity with incidence of diabetes adjusted for age, sex, and current BMI was highly significant (P less than 0.0001). This adjusted incidence of diabetes in cases/1000 person-yr of obesity was 24.8 for people with less less than 5 yr of obesity, 35.2 for people with 5-10 yr of obesity, and 59.8 for people with at least 10 yr of obesity. There was no apparent excess risk of diabetes for people who had a BMI of at least 30 kg/m2 and then lost weight. They had a slightly nonsignificantly higher rate than people who had not attained a BMI of at least 30 kg/m2 and a lower rate than people whose BMI remained 30-35 kg/m2. The relationship of duration of obesity with serum insulin concentrations among nondiabetic people was determined controlling for sex and age, BMI, and plasma glucose concentrations at the time of a glucose tolerance test. Duration of obesity was inversely associated with fasting serum insulin concentration through most of the range of fasting plasma glucose concentrations (P less than 0.001) and tended to be inversely associated with 2-h postload serum insulin concentration through the entire range of postload plasma glucose concentrations (P = 0.058).