This study evaluated B-lymphocyte function in 30 patients following major trauma with frequent screening over a period of 21 days post-trauma. Peripheral blood mononuclear cells (PBMC) were phenotyped with monoclonal antibodies and in vitro B-cell function was tested both for unstimulated cells (spontaneous) and following stimulation with pokeweed mitogen (PWM). The capacity for terminal B-cell maturation into plasma cells was assessed by the number of cells bearing cytoplasmic immunoglobulin (CIg+). Although the number of circulating B cells in the trauma patients was not decreased following injury (12 ± 2%), the number of CIg+ cells was significantly decreased (0.2 ± 0.1 to 3.0 ± 1.5) compared to controls (5 ± 1) up to 21 days post-trauma (p ≤ 0.01).Spontaneous B-cell synthesis of IgA, IgM, and IgG was significantly depressed on day 1, but IgA was within normal range (159 ± 30 ng/ml) by day 3, and IgA levels were supranormal (118 to 300% of control) on days 5–10 before returning to normal on days 14 to 21. Synthesis of IgG was 100 ± 20 ng/ml on day 3 (control, 165 ± 31 ng/ml), and IgG levels were supranormal (+45 to +139%) thereafter. On the other hand, IgM synthesis was decreased on all days studied (120 ± 35 to 220 ± 70 ng/ml) compared to controls (366 ± 105 ng/ml). Synthesis of all Ig subclasses in PWM cultures followed a similar pattern. There was a marked monocytosis (30 ± 2% LeuM3+ PBMC's) compared to control values (13 ± 2% LeuM3± PBMC's). In patients with an increase of monocytes (Mø) of > 30%, PWM-induced IgM synthesis was depressed to 35% of normal values, while IgG was normal and IgA was increased. These data suggest that altered B-cell function following trauma may be due largely to alterations in Mø/T-cell interaction.