Human 'acute-phase' serum amyloid A protein (A-SAA) is a major acute-phase reactant (APR) and an apolipoprotein of high density lipoprotein 3 (HDL3). We have examined several parameters of A-SAA biosynthesis in PLC/PRF/5 hepatoma cells in response to monocyte conditioned medium (MoCM) and dual treatment with interleukin-1 beta and interleukin-6 (IL-1 beta + IL-6). Treatment of PLC/PRF/5 cells with MoCM or IL-1 beta + IL-6 caused a dramatic and rapid increase in A-SAA mRNA and protein synthesis; A-SAA mRNA was first detectable at 3 h, with peak levels reached by 24 h. A-SAA mRNA accumulation is accompanied by a gradual and homogeneous decrease in the length of the A-SAA poly(A) tail; the poly(A) tail shortening does not apparently affect the intrinsic stability of A-SAA mRNA. Analysis of RNA isolated from the ribonucleoprotein, monosome and polysome fractions of cytokine-treated PLC/PRF/5 cells showed that most A-SAA mRNA was associated with small polyribosomes, regardless of time post-stimulus, suggesting that the translational efficiency of A-SAA mRNA is constant throughout cytokine-driven induction. Moreover, the transit time of A-SAA protein out of the cell is also constant throughout the time course of induction. These data provide evidence of a paradox with regard to the transcriptional upregulation of A-SAA by IL-1 beta + IL-6 and the relative synthesis of A-SAA protein and suggest a role for post-transcriptional control of A-SAA biosynthesis during the acute phase.