Objective To test the hypothesis that using handheld cellular telephones is relatedto the risk of primary brain cancer.Design and Setting Case-control study conducted in 5 US academic medical cen-ters between 1994 and 1998 using a structured questionnaire.Patients A total of 469 men and women aged 18 to 80 years with primary braincancer and 422 matched controls without brain cancer.Main Outcome Measure Risk of brain cancer compared by use of handheld cel-lular telephones, in hours per month and years of use.Results The median monthly hours of use were 2.5 for cases and 2.2 for controls.Compared with patients who never used handheld cellular telephones, the multivar-iate odds ratio (OR) associated with regular past or current use was 0.85 (95% con-fidence interval [CI], 0.6-1.2). The OR for infrequent users ( 0.72 h/mo) was 1.0 (95%CI, 0.5-2.0) and for frequent users ( 10.1 h/mo) was 0.7 (95% CI, 0.3-1.4). The meanduration of use was 2.8 years for cases and 2.7 years for controls; no association withbrain cancer was observed according to duration of use (P=.54). In cases, cerebraltumors occurred more frequently on the same side of the head where cellular tele-phones had been used (26 vs 15 cases; P=.06), but in the cases with temporal lobecancer a greater proportion of tumors occurred in the contralateral than ipsilateral side(9 vs 5 cases; P=.33). The OR was less than 1.0 for all histologic categories of braincancer except for uncommon neuroepitheliomatous cancers (OR, 2.1; 95% CI, 0.9-4.7).