SYNOPSISThe subpopulations of T‐lymphocytes and monocytes were studied in 21 Episodic Cluster Headache (ECH) patients, both in and out of the crisis. The following MoAb of the Becton‐Dickinson series were used: Leu1 (pan T cells), Leu2a (suppressor/cytotoxic cells), Leu3a (helper cells), Leu7 (NK cells) and LeuM3 (monocytes). All the subjects were typed for the HLA‐A,B,C and DR antigens of the Human Major Histocompatibility Complex. 10 patients out of 21 were DR5+. Thus, two groups could be distinguished: DR5 + patients and DR5‐ patients. We correlated the variations of the leukocyte subpopulations in and out of the crises with the two groups, since HLA‐DR antigens are related to the immune response.A significant increase of the LeuM3 + cells during the crisis was observed in DR5‐ group (26.2 ± 7.7 vs 18.3 ± 7.1; p<0.05). In the DR5 + group there was an increase of the Leu7 + cells during the crisis (18.1 ± 6.7 vs 12.7 ± 4.9; p<0.05) whereas outside of the crisis the LeuM3 + subpopulation increased (21.9 ± 7.6 vs 18.3 ± 7.1; p<0.02) in the same group. The observed values of the leukocyte subpopulations studied (difference between the data of crisis and out of it) in the two groups were not significantly different. These data confirm our previous studies on Leu7+ and LeuM3 + subsets in ECH patients. Moreover, they allow new speculation about a possible role of Class II antigen