In this paper we discuss recent data concerning immunoreactivity on the one hand to the cartilage derived molecule type II collagen (CII) and on the other hand to the complement factor C1q, in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). By using the ELISPOT method we have been able to show that production of antibodies to CII and to C1q is common in inflamed joints but not in the periphery of RA-patients, whereas production to C1q is commonly seen in the circulation of active SLE patients. Previously an immunological cross-reactivity has been described between these two proteins. The possibility of in vivo cross-reactivity between these two molecules might have consequences for the different disease manifestations in RA and SLE. This paper also stresses the importance of single cell analysis of antibody production when evaluating local antibody production in different body compartments and also when the aim is to assay changes in antibody production over time.