An increase in astrocyte mitogenic factors and in some specific astroglial enzymatic activities after neuronal injury has been observed. Our study is concerned with the effect of the intracerebral administration of ibotenic acid (IBO) into the rat hippocampus. IBO injection causes a selective degeneration of neurons while sparing afferent fibers. We observed a transient increase in glutamine synthetase activity, a well-known astroglial marker, reaching a peak at 9-15 days after injury in lesioned hippocampus. We investigated the presence of astrocyte mitogenic factors at various times after toxin injection. Crude extracts, prepared from lesioned hippocampi 4, 9, and 14 days after IBO injection, were tested for the ability to stimulate [methyl-3H]thymidine incorporation into rat astroglial cell cultures. Crude extracts prepared 9 and 14 days after IBO injection showed a higher mitogenic activity compared to extracts prepared 4 days after lesion. Mitogenic activity of injured brain extracts was suppressed by heat inactivation (100 degrees C for 10 min).