To investigate whether porcine insulin (PI) and human insulin (HI) have different effects on brain functions outside of hypoglycemia, sleep and the sleep EEG were recorded in eight insulin-dependent diabetes mellitus (IDDM) patients in three separate sessions of 2 consecutive nights. Near-normoglycemia was confirmed by measurements of capillary blood glucose before and after sleep and at 0145 hours. The treatment effect (PI compared to HI) consisted of a change in the NREM sleep EEG in the spindle frequency range. Spectral power density in the 14-Hz bin was reduced upon transfer from PI (session 1) to HI (session 2) in all subjects, and increased upon reversal to PI (session 3) in all but one subject. There were no significant treatment effects on any other sleep EEG variable or on sleep stages. The subjects rated their sleep as more sound and their state in the morning as more relaxed during PI treatment. They were, however, not blinded to the type of insulin they were using. Porcine insulin and human insulin may exert differential effects on spindle-generating mechanisms in the thalamocortical system. The results indicate that human insulin may affect brain functions differently compared to animal insulin under near-normoglycemic conditions.