Abstract: A method is provided for detecting up to four classes of oligonucleotides which have been separated by gel electrophoresis. The method entails labeling members of each class of oligonucleotide with dyes selected from separate sets of dyes so that members of the same class are labeled with dyes from the same set. The four sets of dyes of the invention consist of derivatives of fluorescein, 2',7'-dimethoxy-4', 5'-dichlorofluorescein, tetramethylrhodamine, and rhodamine X carboxylic or sulfonic acid, respectively. Dyes from these sets are spectrally resolvable under conditions of gel electrophoresis.