The metabolic, histochemical and ultrastructural modifications induced in rabbit articular cartilage during in vitro incubation at 37 degrees C, for various periods (10 min to 18 h), using Krebs phosphate-glucose nutrient medium, were studied. It was found that after only 10 min of incubation, the chondrocytes increase their synthesis of matrix macromolecules for, at least, the next 6 h. This was suggested by: 1. Increased incorporation 35S-sulfate and 3H-glycine during the first 6 h of incubation. 2. An intensification of metachromasia, which also spread out into the superficial layer that is normally orthochromatic. Only the most superficial layer corresponding to one or two rows of the cells, retained its staining pattern throughout the incubation; 3. A rapidly acquired abundant rough endoplasmic reticulum, enlarged Golgi area and numerous newly synthesized proteoglycan molecules. This study poses fundamental questions about the mechanisms that regulate matrix synthesis by the chondrocytes.