Proinflammatory cytokines help orchestrate host responses to infection and are a major communication link between peripheral immunity and the CNS. These cytokines initiate a number of CNS events that culminate in both physiological and behavioral changes. Peripheral IL-1β also affects information processing. A series of experiments examining the effect of learning intensity, motivation, and cytokine dose are reported. Using a well-established Morris water maze (MWM) system with female C57BL/6 mice, we report that (1) IL-1 (100 ng/mouse, i.p.) has no effect on MWM learning when mice are subjected to a spaced as opposed to a massed learning protocol; (2) water temperature is critical to the IL-1 effect on learning insofar as IL-1 interferes with learning in a warm-water but not a cold-water maze, and (3) higher doses (1,000 ng/mouse, i.p.) of IL-1 in experimental systems known to produce the IL-1-induced learning deficit with lower doses (100 ng/mouse, i.p.) show consistent facilitation, not impairment, of learning.