Brain metastases derived from abdominal neuroblastoma are an uncommon complication of this tumour; however, an increase in their occurrence has recently been reported. In the present study, we have investigated the influence of factors derived from central nervous system glial cells on the proliferation of human neuroblastoma cells (SH-SY5Y) in vitro. Co-culture experiments show that a 24-h exposure to factors released by type 1 astrocytes (A1) may induce a significant decrease in [(3)H]thymidine ([(3)H]TdR) incorporation by SH-SY5Y cells. This effect was not duplicated by fresh A1-conditioned medium (A1-CM); A1-CM became active only when it was heated or frozen. In contrast to this short-lived inhibitory effect, long-term treatment (3, 6 and 9 days) with A1-CM produced a significant and dose-dependent increase in SH-SY5Y cell number. Immunoneutralisation of A1-CM with an anti-transforming growth factor-beta antibody eliminated the inhibitory effect on [(3)H]TdR uptake in SH-SY5Y cells, but did not affect the increased number of viable cells observed after long-term treatments. In conclusion, these results showed that factor(s) released by A1 may affect the proliferation/survival of a human neuroblastoma cell line in vitro inducing: (a) a short transient negative effect on DNA synthesis and (b) an overall sustained trophic action. These results are suggestive of a possible role of glial cells in the establishment of brain metastases of neuroblastomas.