We measured sequential changes in hemoglobin concentration and erythrocyte sedimentation rate in 27 previously healthy children hospitalized for a variety of moderately severe acute inflammatory processes. Among 18 retrospectively studied children, 61% had mild anemia for age on admission, and Hgb values dropped greater than 2 SD in 83% during active inflammation. During recovery, Hgb concentrations spontaneously rose greater than 1.3 gm/dl in 79% of the children. Mean Hgb drop was 1.8 gm/dl in 5.6 days, representing an average noniatrogenic blood loss of 107 ml, among nine prospectively studied children. Only one of these had laboratory evidence of hemolysis, and none had clinical evidence of bleeding or overhydration. Results of both studies combined showed that a mean 13% Hgb drop during active inflammation was followed by a mean 24% Hgb rise during resolution of acute inflammation. We conclude that most children with moderately severe acute inflammation experience a significant drop in Hgb within 1 week of illness onset, regardless of the specific cause of inflammation. In general, this mild to moderate anemia resolves without hematinic therapy.