In fibroblasts, stimulation of receptor tyrosine kinases results in the activation of the extracellular signal‐regulated kinase 2 (ERK2). The major signalling pathway employed by these receptors involves the activation of p21ras and raf‐1 kinase. Here we show that in NIH3T3 and rat‐1 fibroblasts, elevation of the intracellular cAMP level results in the inhibition of ERK2 activation induced by PDGF, EGF and insulin treatment. Analysis of various signalling intermediates shows that cAMP interferes at a site downstream of p21ras, but upstream of raf‐1 kinase. Inhibition by cAMP depends on both the cAMP concentration and the absolute amount of p21ras molecules bound to GTP, suggesting a mechanism of competitive inhibition. Also TPA‐induced, p21ras‐independent, activation of raf‐1 kinase and ERK2 is inhibited by cAMP. We have used the inhibitory effect of cAMP to investigate whether phosphorylation of mSos, a p21ras nucleotide exchange factor, is dependent on the activity of the raf‐1 kinase/ERK2 pathway. We found that phosphorylation of mSos, as monitored by a mobility shift, is delayed with respect to p21ras and ERK2 activation and is inhibited by cAMP in a similar cell type‐ and concentration‐dependent manner as the inactivation of ERK2. These results provide evidence for a model of p21ras‐directed signalling towards ERK2 that feeds back on mSos by regulating its phosphorylation status and that can be negatively modulated by protein kinase A and positively modulated by protein kinase C action.