The relation between the inflammatory cytokine tumour necrosis factor-alpha (TNF or cachectin), which induces acute phase responses, and an established acute phase protein, C-reactive protein, was studied in various infectious and inflammatory diseases in man. All cases with very high serum concentrations of C-reactive protein (150 to 400 mg/l; normal reference value less than 10 mg/l) also had raised serum concentrations of TNF (53 to 705 ng/l; normal reference value less than 40 ng/l). In 19 out of 91 (21%) of the cases, however, a raised TNF concentration without correspondingly raised C-reactive protein concentration was also noted. Conversely, in 23 out of 106 (22%) cases raised C-reactive protein was observed in the absence of a raised TNF concentration. The ratios were high in allograft rejection and low in myocardial infarction and Kawasaki's disease. The highest mean concentration of circulating TNF was found in bacterial infections, graft rejection, and myocardial infarction. It is concluded that although high C-reactive protein concentrations are usually accompanied by raised TNF concentrations, there are pronounced relative variations in the serum concentrations of these proteins in various disease states, suggesting that there may be independent, disease specific regulatory pathways for TNF and C-reactive protein.