The objective of this study is to understand the metabolic and immunologic basis of diabetes in adult blacks with diabetic ketoacidosis (DKA). Twenty- one black adults presenting with DKA ([mean ± SD] blood pH = 7.18 ± 0.09, plasma glucose = 693 ± 208 mg/dl, and positive serum ketones) had a subsequent clinical course of non-insulin-dependent diabetes mellitus (NIDDM). Human leukocyte antigens (HLAs) DR and DQ and antibodies to glutamic acid decarboxylase (GAD) and islet cell cytoplasmic proteins (ICP) were measured to assess autoimmunity. Insulin action was evaluated by the euglycemic insulin clamp, and insulin secretion was measured by C-peptide responses to oral glucose. Ketoacidosis was treated with insulin. Two subjects had a precipitating illness; four had a history of NIDDM. At the time of study, subjects' glycemic control was good (HbA(1c) = 5.7 ± 1.6%). Nine subjects were treated with insulin, and 12 were on either sulfonylurea treatment or diet alone. Men (n = 12) were younger than women (n = 9) (40.8 ± 9.8 and 51.1 ± 6.3 years of age, respectively, P < 0.05) but similar in body mass index (27.8 ± 2.7 and 29.98 ± 4.1 kg/m2, respectively). Antibodies to GAD and ICP were absent. All but one subject was insulin resistant compared with normal subjects (glucose disposal 3.56 ± 0.04 vs. 6.86 ± 0.02 mg · kg-1 · min-1), and insulin secretion was lower. HLA DR3 and DR4 frequency was higher than in nondiabetic black control subjects (65 vs. 30%, P < 0.012). We conclude that black adults presenting with DKA have a subsequent clinical course and metabolic features (insulin resistance in the presence of good glycemic control and continued C-peptide response) characteristic of NIDDM. The absence of GAD or ICP antibodies makes β-cell autoimmune destruction unlikely. The increased frequency of HLA DR3 and DR4 suggests genetic components of insulin-dependent diabetes mellitus (IDDM) and NIDDM.