In serum-free monolayer cultures of early postnatal weaver (wv/wv) cerebellum granule neurons show decreased attachment, survival and neurite outgrowth when compared to wild-type (+/+) littermate cultures. wv/wv Astrocytes display a more epithelioid morphology and altered proliferation. However, both morphology and proliferation of wv/wv astrocytes were reversed to a normal phenotype by addition of purified small neurons from early postnatal cerebella from +/+ animals. Attachment of +/+ neurons to wv/wv astrocytes was not significantly different from that of +/+ astrocytes and antigenic marker profiles of wv/wv and +/+ astrocytes differed only slightly. Attempts failed to revert the abnormal wv/wv phenotype in neurons by addition of gangliosides, triiodothyronine T3, prostaglandin A2, medium containing 1% horse serum, conditioned medium from +/+ cerebellar cultures, or by cocultivation with +/+ astrocytes. We would like to suggest that the primary defect of the wv/wv mutation is predominantly an abnormality in granule cell neurons, but not of the vast majority of astrocytes.