We examined patient knowledge as a moderator of psychological reactions to illness among patients with insulin-dependent diabetes mellitus. We reasoned that knowledgeable patients would have the most severe reactions to their illness because the causal implications of good or poor metabolic control would be most apparent. Accordingly, we expected that more knowledgeable patients would react more negatively than less knowledgeable patients to poor metabolic control but would react more positively to good metabolic control. Results from a sample of 46 patients with insulin-dependent diabetes mellitus supported this hypothesis. These findings suggest that increased patient knowledge may not produce uniformly positive results. Patient education programs must consider the psychological implications of patient knowledge in addition to the physiological consequences.