In a study sample of second generation Japanese American men (age range 45-74 years), family history of diabetes in a sibling or parent was present in 69 men (24 of 79 normal men and 45 of 78 type 2 diabetic men, P less than 0.001). Both general adiposity and body fat distribution have been associated with type 2 diabetes. Our hypothesis was that the association of both overall adiposity and of larger specific regional fat deposits with type 2 diabetes would differ depending upon family history. The relationships between diabetes and differences in general adiposity (whether current or maximum lifetime body mass index or BMI, sum of skinfolds, or sum of computed tomography or CT fat areas) and between diabetes and body fat distribution (measured as abdominal and thigh circumferences, cross-sectional body fat areas by CT of thorax, abdomen, and thigh, and skinfold thicknesses of triceps, biceps, forearm, chest, subscapula, abdomen, and thigh) were more apparent in those men without a family history of diabetes than in those with a family history. In men without a family history, diabetic men had significantly higher values for several variables which assessed overall adiposity: current BMI (P less than 0.001), maximum lifetime BMI (P less than 0.001), sum of skinfolds (P less than 0.006), and sum of CT fat areas (P less than 0.015). In addition several measurements of upper truncal adiposity were significantly increased in diabetic men: abdominal circumference (P less than 0.004), thoracic (P less than 0.015) and abdominal (P less than 0.03) subcutaneous CT fat areas, intra-abdominal CT fat areas (P less than 0.001), and chest (P less than 0.03) and subscapular (P less than 0.0002) skinfold thicknesses. The results pertaining to those without a family history appear to be due to increased adiposity and associated larger specific regional fat depots leading to diabetes and lesser adiposity and smaller amounts of fat in the same regional depots protecting against diabetes.