Neopterin (N), a marker for activated cell-mediated immunity, was assayed in the sera of 44 lung recipients early and late after transplantation. The study was a prospective, blind clinical trial designed to evaluate the following: (1) the daily dynamics of the serum neopterin/creatinine (N/C) ratio during the first 3 weeks after transplantation; (2) the correlation between changes in the serum N/C ratio and episodes of rejection or infection; (3) the correlation between the serum N/C ratio and the concentration of serum soluble interleukin 2 receptor (sIL-2R), a marker of T-cell activation; and (4) the potential value of monitoring the serum N/C ratio during noninvasive long-term follow-up of lung recipients.Sera from lung recipients were collected every day or every 2 days for the first 3 weeks after transplantation (22 patients) and before fiberoptic bronchoscopy and routine consultation (44 patients). The N concentrations were determined by radioimmunoassay and sIL-2R levels were measured using a sandwich enzyme immunoassay.Serum N/C is an early and sensitive marker of immune activation in the 21 days following transplantation. The N/C ratios during early rejections (815 +/- 182 mumol/mol) and infections (677 +/- 75 mumol/mol) were higher than those in patients with no complications (160 +/- 32 mumol/mol). In contrast, the N/C ratio did not increase during rejection later after transplantation. More than 3 weeks after transplantation, an increase in the N/C ratio was specifically correlated with infections, mainly those due to cytomegalovirus (CMV) (control subjects, 132 +/- 12 mumol/mol; rejections, 163 +/- 25 mumol/mol; CMV pneumonia, 786 +/- 103 mumol/mol, p < 0.001). The N/C ratio correlated with sIL-2R serum levels (r = 0.625, p < 0.001).Our results indicate that more than 3 weeks after transplantation, the serum N/C ratio increases only in cases of infection, mostly CMV pneumonia. In contrast, both rejection and infectious complications are associated with an increased N production in the early postoperative period.