The numbers of resident peritoneal cells recovered from NZB and (NZB × NZW)F₁ hybrid mice, which develop systemic lupus erythematosus (SLE), increased strikingly with age as compared with cells recovered from normal mice. The rise paralleled the onset of anti‐DNA antibodies, occurring earlier in females than in males. The increased number of cells was due to an accumulation of medium‐sized cells with an indeterminate appearance, but with the functional characteristics and cell markers typical of a macrophage. The unusual cells were esterase, F4/80 and Mac‐1 positive, peroxidase, and Alcian blue negative, and were shown on sedimentation velocity separation to be phagocytic for EA and C3 (serum‐treated) zymosan; 47–48% of peritoneal cells were la positive.