The on-chip generation of dynamic chemical signals in a flow stream via pulse code modulation (PCM) is demonstrated. In this chip the output signal concentration is determined by dispersion and averaging of a serial stream of digitally encoded plugs of concentrated solute and pure solvent as the plugs flow through a long dispersive capillary. A two-bit PCM chemical signal generator was fabricated in two-level PDMS technology. The chip was capable of generating 31 distinct output levels with 10-plug cycles. Several example chemical waveforms (sawtooth and cosine) were generated at flow rates of 43.2 nL s−1, and plug frequencies of up to 15 Hz, with maximum output signal bandwith of up to about 1 Hz. The modulator chip was also used to synthesize physiological signals emulating intracellular β-cell cytosolic Ca2+ oscillations, extracellularβ-cell insulin release and rat-striatum dopamine release.