In this study, we investigated a pattern-recognition technique based on an artificial neural network (ANN), which is called a massive training artificial neural network (MTANN), for reduction of false positives in computerized detection of lung nodules in low-dose computed tomography (CT) images. The MTANN consists of a modified multilayer ANN, which is capable of operating on image data directly. The MTANN is trained by use of a large number of subregions extracted from input images together with the teacher images containing the distribution for the "likelihood of being a nodule." The output image is obtained by scanning an input image with the MTANN. The distinction between a nodule and a non-nodule is made by use of a score which is defined from the output image of the trained MTANN. In order to eliminate various types of non-nodules, we extended the capability of a single MTANN, and developed a multiple MTANN (Multi-MTANN). The Multi-MTANN consists of plural MTANNs that are arranged in parallel. Each MTANN is trained by using the same nodules, but with a different type of non-nodule. Each MTANN acts as an expert for a specific type of non-nodule, e.g., five different MTANNs were trained to distinguish nodules from various-sized vessels; four other MTANNs were applied to eliminate some other opacities. The outputs of the MTANNs were combined by using the logical AND operation such that each of the trained MTANNs eliminated none of the nodules, but removed the specific type of non-nodule with which the MTANN was trained, and thus removed various types of non-nodules. The Multi-MTANN consisting of nine MTANNs was trained with 10 typical nodules and 10 non-nodules representing each of nine different non-nodule types (90 training non-nodules overall) in a training set. The trained Multi-MTANN was applied to the reduction of false positives reported by our current computerized scheme for lung nodule detection based on a database of 63 low-dose CT scans (1765 sections), which contained 71 confirmed nodules including 66 biopsy-confirmed primary cancers, from a lung cancer screening program. The Multi-MTANN was applied to 58 true positives (nodules from 54 patients) and 1726 false positives (non-nodules) reported by our current scheme in a validation test; these were different from the training set. The results indicated that 83% (1424/1726) of non-nodules were removed with a reduction of one true positive (nodule), i.e., a classification sensitivity of 98.3% (57 of 58 nodules). By using the Multi-MTANN, the false-positive rate of our current scheme was improved from 0.98 to 0.18 false positives per section (from 27.4 to 4.8 per patient) at an overall sensitivity of 80.3% (57/71).