Male Wistar rats were treated with paracetamol (200 mg/kg twice a day) for 2, 3, 4 and 9 weeks. During the first four weeks of paracetamol administration the serum sulfate concentration was significantly decreased. However, during the fourth until the ninth week, the serum sulfate concentration was only diminished to a small and insignificant extent. The paracetamol administration did not lead to serious liver or renal toxicity, as determined by alanine aminotransferase and creatinine levels in the serum of the rats. The paracetamol-induced serum sulfate depletion, observed during the first four weeks of the experiment, led to a significantly lower glycosaminoglycan content of the patellar cartilage of the rats after three and four weeks paracetamol treatment. When after the fourth week the serum sulfate concentration rose to nearly normal levels also the glycosaminoglycan content in the rat patellar cartilage reached control levels. These data indicate that the serum sulfate depletion might be the causative factor for the observed reduction in glycosaminoglycan content of rat patellar cartilage.