In this report we describe an in vitro masking action of IgM rheumatoid factor (IgM-RF) towards IgG antinuclear antibodies (IgG-ANA) which can be recovered by using D-penicillamine (DP) as an unmasking agent. The mechanism of this masking effect was elucidated by using smears of rat free nucleus as substrate, instead of the classical rat liver cryostat sections technique. It was postulated that the 'inhibition' of IgG-ANA by IgM-RF may be due to the formation of high molecular weight complexes (HMWC); this would be the same in vivo. Allowing the formation of HMWC which can be removed from the circulation, IgM-RF may have a protective effect by preventing or minimizing systemic lesions. Therefore, IgM-RF may be considered as a defence response against potentially noxious ANA or antigen-antibody complexes. Induced nephropathy and the high frequency of detection of ANA observed in rheumatoid arthritis (RA) patients treated by DP may be the result of the dissociating effect of this drug on HMWC, in which the activity of pre-existing ANA is hidden when rat liver sections are used for its detection.