Patients with renal cell carcinoma (RCC) can exhibit fever, weight loss and increases in acute phase proteins. Interleukin (IL)-1, tumour necrosis factor (TNF) and IL-6 are considered major mediators of local and systemic inflammation. We measured plasma IL-1 beta, TNF-alpha (immunoradiometric assay) and IL-6 (ELISA) in 78 consecutive patients with untreated RCC and in 56 normal subjects. IL-6 plasma levels were higher in patients with RCC (mean 24.2 pg/ml, 11.1-37.3, 95% confidence interval) than in normal subjects (11.6 pg/ml, 10.1-13.1, n = 39, P < 0.01). The patients with fever or weight loss had higher blood levels of IL-6. IL-6 blood levels were also higher in patients with lymph node invasion and/or distant metastases (94.7 pg/ml, 39.0-150.4, n = 15) than in patients with undisseminated RCC (7.4, 4.1-10.7, n = 63, P < 0.0001). An abnormal IL-6 plasma value (> 40 pg/ml) had a positive predictive value of 91.0% for lymph node and/or metastatic spread of RCC. IL-6 was statistically correlated with C-reactive protein (nephelometric assay) blood values r' = 0.67, n = 78, P < 0.001). The TNF-alpha and IL-1 beta levels were not significantly different in patients with or without fever or weight loss. The plasma levels of the three cytokines were not correlated with the size of the primary tumour. An increased plasma value of IL-6 is a good marker for tumour dissemination in patients with untreated RCC.