Peripheral blood lymphocytes from 20 patients with acute infectious mononucleeosis (IM) were studied for cell aggregation and for cap formation by concanavalin A (Con A). The lymphocytes from these patients showed 5.2+/-1.5% cells with a Con-A-induced cap and a high degree of cell aggregation without Con A, compared to 27.7+/-3.2% caps and a low degree of cell aggregation with normal lymphocytes. The lymphocytes from IM patients were fractionated to enrich for T and B cells. There was a low frequency of cap formation in both T and B cells, but the high degree of celll aggregation without Con A only occurred with B cells. Studies with four patients in clinical remission from acute IM have shown that the frequency of Con-A-induced cap formation only returned to normal more than 3 months after the beginning of clinical remission and that even at 6 months the cells still showed a high degree of cell aggregation. The results indicate that a high degree of B-cell aggregation and a low percentage of B and T cells with a Con-A-induced cap were associated with acute IM and that the changes associated with a high degree of B-cell aggregation were by themselves not sufficient to cause the disease.