In an effort to find out if the use of non-human primate pancreas may improve the sensitivity of the islet cell antibody (ICA) test, the sera from patients with type 1 diabetes (insulin-dependent IDDM) and controls were investigated by indirect immunofluorescence (IFL) on both human and baboon substrates. The mean titers of positives were insignificantly higher (1:24.9) on baboon as compared to human tissue (1:22.3). Of 50 sera from IDDM patients positive for ICA on human tissue, 47 were also positive on baboon pancreas. Of 40 ICA-negative IDDM sera two were judged positive on baboon substrate. ICA were positive on human/baboon pancreas in 3/4 out of 50 first-degree relatives of IDDM patients, 2/2 of 50 sera from patients with autoimmune diseases, 0/0 of 50 sera from type 2 diabetics and 2/1 of 100 mixed hospital controls. A disadvantage of baboon pancreas for ICA testing by IFL is the high background fluorescence given by the exocrine pancreas. With baboon tissue, three highly positive results would have been missed with undiluted sera which are usually used in this assay. It is therefore suggested that human pancreas should still be preferentially used for ICA determination, but baboon tissue may be a valuable substitute.