Three proposed chondroprotective agents (CP), namely glucosamine sulfate (GAS), chondroitin sulfate (CS) and glycosaminoglycan-peptide complex (GP-C), were tested on differentiated human articular chondrocytes cultured in clusters. Chondrocyte productions of proteoglycans (PG), type II collagen (coll. II) and prostaglandin E2 (PGE2) were established by specific radioimmunoassays applied to the culture medium (CM) and in chondrocyte clusters (CC). Collagenolytic activity was assayed in CM. DNA synthesis, studied by measuring 3H-thymidine incorporation, was unaffected by CS and GAS. GP-C, at low concentration, stimulated DNA synthesis. GP-C, at higher doses, induced a high increase in PG and coll. II productions. GAS and CS induced a stimulatory effect limited to PG production. None of the CP tested here affected the basal PGE2 production by human chondrocytes