To determine if patients with head and neck squamous cell carcinoma represent an appropriate population for immune reconstitution with thymosin alpha 1, leukocyte migration inhibition (LMI) in response to phytohemagglutinin was measured in 24 previously untreated patients with head and neck cancer, and the in vitro effects of thymosin alpha 1 on migration inhibition were assessed. Compared to normal subjects, LMI was impaired in the head and neck cancer patients. Thymosin alpha 1, in vitro, was associated with improvement in LMI in the cancer patients. Improvements in migration response with thymosin alpha 1 appeared to be independent of levels of various T-lymphocyte subpopulations. However, patients with a normal LMI response had lower suppressor/cytotoxic cell levels than normal subjects or patients with impaired LMI. The findings confirm prior reports of the effects of thymic hormones on lymphokine production in vitro and provide rationale for further clinical studies of thymosin alpha 1 in patients with head and neck squamous cell carcinoma.