Hochuekkito is a traditional Japanese and Chinese medicine for the treatment of elderly patients with general weakness. Fifteen elderly patients participated in this study. A multicentre, prospective, randomised, double-blind, placebo-controlled study with n-of-one and responder-restricted design was performed. After the run-in period, the patients were divided into responders and non-responders. Only responders were entered in the study and were randomised into three groups: an active–placebo group, a placebo–active group and an active–active group. The study consisted of two 6-week terms with a 2-week washout period in between. The SF-36 and Profile of Mood States (POMS) were assessed. In addition the biodefence status was evaluated by measuring the natural killer cytolytic activity (NK activity), interleukin 2 - producing activity of peripheral lymphocytes, lymphocyte proliferating activity and lymphocyte cell-surface antigens. The physical component summary of the SF-36 analysis significantly improved in the Hochuekkito-treated group. Four components (A–H, anger–hostility; F, fatigue; T–A, tension–anxiety; C, confusion) out of six improved in the Hochuekkito-treated group in the POMS analysis. Lymphocyte proliferating activity improved in the Hochuekkito-treated group but not significantly. Concerning the surface antigens of peripheral lymphocytes, the population of CD3 positive cells and CD3CD4 double positive cells increased in the Hochuekkito-treated group.