Cyclic neutropenia (CN) is an inherited disease known to occur in both humans and Gray Collie dogs. In dogs, the disease is characterized by a profound and cyclic decrease in circulating granulocytes at 12-day intervals. Other formed elements of the blood also show cyclic changes and thus the disease is also called cyclic hematopoiesis (CH). In this study, daily serum levels of lysozyme and a factor with macrophage migration inhibitory (MIF) activity were assayed. Both MIF activity and lysozyme levels were elevated more than 2-fold and fluctuated cyclically in CH dogs during the 12-day cycle: CH dogs CH 490 and CH 491, had 32.7 +/- 16.8% and 35.9 +/- 18.3% migration inhibitory activity, respectively, as compared to 15.1 +/- 1.4% in normal dog N 492; CH 490 and CH 491 had 78.7 +/- 43.7 units and 86.9 +/- 58.7 units of lysozyme, respectively, as compared to 33.4 +/- 1.7 units in N 492. The change of MIF activity tended to precede that of lysozyme activity in CH dogs. Furthermore, MIF levels and monocyte counts correlated significantly during the 12-day neutropenia cycle (CH 490, r = 0.677, P less than 0.001; CH 491, r = 0.583, P less than 0.01).