This study introduces an integrated algorithm based on the Walsh transform to detect interictal spikes and artifactual data in epileptic patients using recorded EEG data. The algorithm proposes a unique mathematical use of Walsh-transformed EEG signals to identify those criteria that best define the morphologic characteristics of interictal spikes. EEG recordings were accomplished using the 10-20 system interfaced with the Electrical Source Imaging System with 256 channels (ESI-256) for enhanced preprocessing and on-line monitoring and visualization. The merits of the algorithm are: (1) its computational simplicity; (2) its integrated design that identifies and localizes interictal spikes while automatically removing or discarding the presence of different artifacts such as electromyography, electrocardiography, and eye blinks; and (3) its potential implication to other types of EEG analysis, given the mathematical basis of this algorithm, which can be patterned or generalized to other brain dysfunctions. The mathematics that were applied here assumed a dual role, that of transforming EEG signals into mutually independent bases and in ascertaining quantitative measures for those morphologic characteristics deemed important in the identification process of interictal spikes. Clinical experiments involved 31 patients with focal epilepsy. EEG data collected from 10 of these patients were used initially in a training phase to ascertain the reliability of the observable and formulated features that were used in the spike detection process. Three EEG experts annotated spikes independently. On evaluation of the algorithm using the 21 remaining patients in the testing phase revealed a precision (positive predictive value) of 92% and a sensitivity of 82%. Based on the 20- to 30-minute epochs of continuous EEG recording per subject, the false detection rate is estimated at 1.8 per hour of continuous EEG. These are positive results that support further development of this algorithm for prolonged EEG recordings on ambulatory subjects and to serve as a support mechanism to the decisions made by EEG experts.