Sponges (Porifera) are nerve- and muscleless. Nevertheless, they react to external stimuli in a coordinated way, by body contraction, oscule closure or stopping pumping activity. The underlying mechanisms are still unknown, but evidence has been found for chemical messenger-based systems. We used the sponge Tethya wilhelma to test the effect of γ-aminobutyric acid (GABA) and glutamate (l-Glu) on its contraction behaviour. Minimal activating concentrations were found to be 0.5 μM (GABA) and 50 μM (l-Glu), respectively. Taking maximum relative contraction speed and minimal relative projected body area as a measure of the sponge’s response, a comparison of the dose–response curves indicated a higher sensitivity of the contractile tissue for GABA than for l-Glu. The concentrations eliciting the same contractile response differ by about 100-fold more than the entire concentration range tested. In addition, desensitising effects and spasm-like reactions were observed. Presumably, a GABA/l-Glu metabotropic receptor-based system is involved in the regulation of contraction in T. wilhelma. We discuss a coordination system for sponges based on hypothetical chemical messenger pathways.