Our objective was to assess the effects of methadone use on immune parameters. A convenience sample of men and women drug injectors who knew their HIV serostatus were enrolled in a longitudinal observational study of HIV illness. During analysis of baseline data, differences were noted in immune parameters among Methadone users. Study participants were recruited in Manhattan, New York, from a methadone maintenance clinic, an infectious disease clinic of an inner city hospital, and a drug-free community center. The participants were 220 men and women, current or former drug injectors, approximately half of them HIV-antibody positive and the rest HJV-antibody negative. Candidates with opportunistic infections and secondary neoplasms were excluded. Methadone users were compared to nonmethadone users for absolute and percentage counts of CD4, CD8, and activated T lymphocytes; CD4/CD8 ratio; an HIV symptom check list; and medical staging. The results discussed in this paper were formulated after data collection was complete. Our data indicate that methadone treatment, while not significantly affecting absolute CD4 lymphocyte count, is associated with a lower CD4 percentage and CD4/CD8 cell ratio, and with a higher CD8 absolute count and percentage. These differences are present regardless of HIV serostatus. Our findings should be interpreted with caution since we did not set out to investigate the effects of methadone on the immune system. Nevertheless, if it is corroborated that methadone has a detrimental effect on the immune system, finding allernatives to methadone-maintenance treatment for drug injectors will be a necessity.