Investigations in the BB rat and the non-obese diabetic (NOD) mouse have provided substantial evidence for the involvement of the monocyte/macrophage system in the development of type 1 diabetes mellitus. However, it is not known whether monocytes play the same role in the pathogenesis of human type 1 diabetes. We investigated this problem in a longitudinal study of 29 recent-onset type 1 diabetes mellitus patients. Monocyte chemotaxis, phagocytosis and superoxide production as well as metabolic and haematological parameters were studied immediately after diagnosis and 6 months later. At diagnosis the patients had activated casein and C5a chemotaxis (casein 70 +/- 9 versus 150 +/- 5 (mean +/- s.e.m.), P < 0.001; C5a 137 +/- 10 versus 158 +/- 5, P < 0.05 (activation immobilizes monocytes, reducing the measured values)), and activated superoxide production (3.6 +/- 0.3 versus 3.0 +/- 0.3, P < 0.05). After 6 months casein chemotaxis (115 +/- 16 versus 150 +/- 5, P < 0.05) and Candida phagocytosis (3.3 +/- 0.1 versus 2.8 +/- 0.2, P < 0.001) were still activated. There was no correlation with other clinical or paraclinical parameters. We conclude that the circulating monocytes in newly diagnosed type 1 diabetes patients are activated. It is reasonable to expect that monocytes at the local site of inflammation in pancreas are even further activated. This could play a pathogenic role in beta cell destruction.