An amber mutation in the secA gene of Escherichia coli causes a pleiotropic decrease in the synthesis of secreted proteins, including maltose-binding protein (MBP) and alkaline phosphatase. Reversal of the inhibition of MBP synthesis in secA(Am) strains by signal sequence mutations in the malE gene has been reported. These results suggest a coupling between secretion and translation which involves an interaction between the signal sequence of nascent polypeptides and a cellular secretion machinery. Further analysis reported here indicated that signal sequence mutations of MBP or alkaline phosphatase did not selectively overcome the inhibition of MBP or alkaline phosphatase synthesis in secA(Am) strains. Rather, at a given time in parallel experiments there was substantial variability among closely isogenic secA(Am) strains in the magnitude of the synthesis block; this variability could account for the earlier results. Further experiments suggested that the inhibition of MBP synthesis in secA(Am) strains was caused by depletion of cyclic AMP, leading to decreased transcription of the malE gene. However, the secretion defects in secA(Am) strains were not affected by cyclic AMP levels. Therefore, we conclude that the reduction in MBP synthesis was a secondary consequence of the primary export defect in the secA(Am) strains.