The proliferative response of preparations of whole PBMC populations from 20 healthy individuals and 28 multiple sclerosis (MS) patients to purified protein derivative (PPD) and myelin basic protein (MBP) was monitored in a kinetic assay over a period of up to 10 days. PPD produced a classical secondary response in both groups, the magnitude being significantly reduced in the MS cohort. The magnitude and pattern of response to MBP did not differ between the two populations. The kinetic profile characteristic of a primary response was observed in both groups. Enrichment of the CD45RO+ve and CD45RA+ve T-cell subsets in PBMC led to a secondary response to PPD in the RO+ve and primary response in the RA+ve population in both groups. The response to MBP in both RO+ve and RA+ve populations exhibited primary kinetics in both MS patients and healthy individuals. However, the use of T-cell subset enriched populations allowed a finer dissection of the response to MBP which highlighted the more active role of RO-positive cells in MS patients. The most striking difference between patients and healthy individuals occurred on day 4 of culture when a greater response to MBP occurred in the CD45RO enriched population, paralleling the response to PPD, in the majority of patients. Futhermore in 4/8 patients and only 1/8 healthy individuals the response in the RO+ve cultures was maintained at a higher level than that seen in the corresponding RA+ve cultures throughout the culture period. This data indicates that a measurable memory response to MBP exists in MS patients implying prior activation of MBP reactive T lymphocytes during the course of disease.