It has become increasingly clear that immune cytokines have an effect on growth and differentiation in the nervous system as well as in the immune system. We have previously reported that interleukin-2 (IL-2) promotes survival of primary cultured neurons from fetal rat brain. In the present study, we investigated the effects of IL-2 as well as IL-6, one of the neurotrophic cytokines, on neuronal morphology and regeneration after damage in primary cultured hippocampal neurons. For neuronal morphology, IL-2 significantly promoted the elongation and branching of neurites, but IL-6 enhanced only the elongation. The neurite-elongating effect of IL-2 was different from that of IL-6 in terms of both effective concentration and maximal effect. In laser beam-damaged neurons, IL-2 significantly increased both the number and the length of branches emerging from the proximal part of damaged neurite. IL-2 also increased the length and the number of non-damaged neurites. IL-6, however, did not affect any of these parameters in damaged neurons. These results suggest that IL-2 and IL-6 modulate neuronal morphology through distinct mechanisms.