In an attempt to detect disease-associated genetic variations and/or exogenously induced alterations in DR2 haplotypes of narcolepsy patients, primed lymphocytes (PLs) were generated in nine families against DR2 haplotypes of narcolepsy patients and healthy family members. Twenty-four PL reagents were obtained and restimulated by cells of unrelated narcolepsy patients and DR2/Dw2-positive healthy individuals. The mean restimulation rates triggered by cells of patients or healthy controls, respectively, never differed significantly. In primary MLC as well as PLT combinations of patients and their HLA-identical siblings no significant stimulation was observed in both directions. We conclude that narcolepsy-specific alterations of class II molecules cannot be cellularly detected or do not exist on peripheral lymphocytes.