Congenital retardation of renal development may increase the risk of renal disease, and this risk may be enhanced by diseases, such as diabetes, that damage the kidney. In this study, the prevalence of urinary albumin excretion, determined in 308 Pima Indians with type 2 diabetes, was 63% in subjects with low birth weight (<2,500 g), 41% in those with normal birth weight (2,500-4,499 g), and 64% in those with high birth weight (> or =4,500 g). When examined as a continuous variable by generalized additive logistic regression, birth weight had a U-shaped association with the prevalence of elevated urinary albuminuria (p = 0.04) after adjustment for age, sex, duration of diabetes, glycosylated hemoglobin, and blood pressure. The odds of elevated albuminuria in subjects of low birth weight was 2.3 times (95% confidence interval 0.72-7.2) that in subjects of normal birth weight, and the odds in subjects of high birth weight was 3.2 times (95% confidence interval 0.75-13.4) as high. Sixty-four percent of the subjects with high birth weight and none of those with low birth weight were offspring of diabetic mothers. After maternal diabetes during pregnancy was controlled for, the odds of elevated albuminuria in subjects of high birth weight was no longer higher (odds ratio = 1.0, 95% confidence interval 0.22-4.9). The higher prevalence of elevated albuminuria in diabetic Pima Indians with high birth weight may be due to intrauterine diabetes exposure, whereas the higher prevalence in those with low birth weight may be due to the effects of intrauterine growth retardation.