Quantification of islet cell antibodies is used increasingly to evaluate pre-clinical Type 1 (insulin-dependent) diabetes mellitus. If expression of the antigen(s) reacting with islet cell antibodies varies depending upon the functional state of the pancreatic islets, this may partly explain differences in assay sensitivity between laboratories. To address this question we altered Beta-cell function in Osborn-Mendel rats, by dietary manipulation prior to killing. Rats were fed chow (n = 7) or a high sucrose/high fat "cafeteria" diet (n = 8) or were fasted for 18 h (n = 6) until immediately prior to killing. Using frozen sections of these rat pancreata in the indirect immunofluorescent test for islet cell antibodies, we determined the end-point titre for 18 sera in which islet cell antibodies had been previously quantified in our standard human pancreas assay. These sera included ten positive sera and eight normal negative control sera. The four most strongly positive sera gave significantly higher end-point titres on "cafeteria" diet-fed pancreata and lower titres on fasted pancreata (p less than 0.04 to 0.002). None of non-diabetic control sera were positive on any substrate. These data suggest that islet antigen expression is increased when Beta-cell function is increased by dietary manipulation. Improved sensitivity in the islet cell antibody assay might be possible by altering Beta-cell function before or immediately after pancreas collection.