No feasible screening instrument is available for early detection of children with autism in Taiwan. The existing instruments may not be appropriate for use in Taiwan due to different health care systems and child-rearing cultures. The purpose of this study was to develop and test a screening questionnaire for generic autism. The initial 18-item screening questionnaire was developed by a child psychiatrist using face-to-face interviews with 10 families of children with autism and then tested on a sample of families of 18 children with autism and of 59 typically developing children. Of these 18 items, 15 had fair or better item discrimination (kappa >0.20) and were selected for the revised screening questionnaire. In the revised questionnaire, cutoff scores of 5 and 6 offered 100% sensitivity and 96.5% specificity, with the area under the receiver operating characteristic curve of 0.983. The revised screening instrument has high sensitivity and specificity, making it potentially useful for screening Taiwanese children at risk for autism. This instrument should be further tested in a population-based study.