Hydrocoele is common in men in Wuchereria bancrofti-endemic areas, the treatment for which is currently surgical intervention. Two community studies have recently suggested that the antifilarial drug diethylcarbamazine (DEC) may have a beneficial effect of reducing the size of hydrocoeles of filarial origin. To test this hypothesis, a double-blind, placebo-controlled study was carried out in 1998 and 1999 in an area of northeastern Tanzania where microfilaria (mf) carrier rates and hydrocoele prevalence rates were known to be high. Ninety-eight adult male volunteers (aged ≥ 15 years) with chronic hydrocoele received DEC 300 mg per day for 12 days (49 patients), or placebo (49 patients). Circumferential and ultrasonographic measurements of the scrotum, and a serum sample for measuring W. bancrofti antigen, were obtained at the onset and after 3, 6 and 12 months. Scrotal size and hydrocoele fluid volume indices were calculated. No statistically significant differences in volumetric measurements between the DEC and placebo groups were found at any of the follow-ups. Separate analyses dividing patients by antigen status, hydrocoele size or presence of thickening of the scrotal skins gave similar results. Geometric mean intensity of W. bancrofti antigen was significantly lower in the DEC group than in the placebo group (P = 0.008), indicating that lack of compliance was not a significant factor. Two months into the treatment trial, mass treatment with monthly low-dose DEC was given to the rest of the community. We conclude that DEC is not effective in reducing the size of hydrocoele of filarial origin. Interventions to replace or supplement hydrocoelectomy should be investigated.