The spontaneous locomotor behavior of rats receiving subcutaneous administration of either acidic or basic fibroblast growth factors was recorded in an activity cage. We report that doses between 1 and 100 micrograms/kg significantly decreased the horizontal and vertical activity, as well as the exploratory and stereotypy behavior of the rats. These effects of fibroblast growth factors seem to be specific since (i) they were cancelled by protein hydrolysis and anti-fibroblast growth factor antibodies, (ii) they were unrelated to their hypotensive activity and (iii) they were not attributable to their high structural similarity with the cytokine interleukin-1. Thus fibroblast growth factors did not show any thermogenic activity, did not affect the hypothalamic output of corticotropin-releasing factor and did not change the plasma levels of corticosterone. Pretreatment of the rats with a specific inhibitor of brain nitric oxide synthase prevented the effects of fibroblast growth factors, suggesting the involvement of nitric oxide in these behavioral modifications. Our results contribute to the accumulating evidence describing non-mitogenic activities of fibroblast growth factors.