Anal cancer associated with human immunodeficiency virus (HIV) infection is an unusual clinical situation in which the appropriate management remains unclear. Experience of treatment and follow-up is presented of six patients with histologically confirmed invasive epidermoid anal cancer on a background of HIV infection. Durable complete responses with acceptable toxicity occurred in two patients with moderate immunosuppression and Stage I-II tumours treated with a combination of concomitant chemotherapy (5-fluorouracil and mitomycin-C) and pelvic radiotherapy (45 Gy in 25 fractions). One patient treated with radiotherapy alone (60 Gy in 30 fractions in two phases) had a complete response. Two patients, one with Stage III tumour and the other with pre-existing acquired immunodeficiency syndrome, died within 6 months of treatment. Moderate to severe perianal skin reactions commonly occurred. Although the world experience of managing anal cancer in HIV infected individuals is small, this and other reports support the use of chemoradiotherapy in selected patients. The appropriate treatment of patients with more advanced tumours and/or advanced HIV infection is uncertain.