This study has shown that glycosaminoglycans added to the culture medium may affect neurite formation in SH-SYSY neuroblastoma cells. The most effective glycosaminoglycans are heparin and COS 8, a preparation with low anticoagulant activity. Promotion of neuritogenesis was remarkable at concentrations as low as lo-' and lo-''. When added at lob4 M both agents are inhibitory. Chondroitin-4 sulfate, dermatan sulfate, and heparan sulfate were also effective, the doses required were, however, as high as M for promoting and M for inhibiting neuritogenesis. Thereby low doses of glycosaminoglycans promote, while higher doses inhibit neurite formation. The effects were observed when neuritogenesis was promoted in neuroblastoma cultures either by deprivation of serum or by addition of retinoic acid, in the former case neuritogenesis occurred within 48 hr; in the latter, in 14 days. PC12 pheochromocytoma cells neuritogenesis was triggered by adding NGF to the culture medium. We have also observed that glycosaminoglycan supplementation to the culture medium lowered the quantity of NGF required to form neurites by PC12 cells. Glycosaminoglycans at the dose of lo-' M allow the formation of PC12 neurites even in presence of 1 ng/ml NGF, a dose that normally is ineffective.