The subthalamic nucleus (STN) is a key component of the basal ganglia, thought to play a central role in the control of normal movement. In Parkinson’s disease (PD) and in dopamine depleted animal models of PD, STN neurones are overactive and show synchronised oscillatory activity. As lesion or deep brain stimulation of STN can alleviate symptoms, this aberrant neuronal activity may be fundamental to expression of PD. Single unit extracellular recordings were made from up to 3 spontaneously firing STN neurones simultaneously, in 300μm thick parasagittal slices of mouse ventral midbrain, perfused with aCSF at 32^oC. Eight mice were treated 10-21 days previously with the dopamine neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) i.p., using the regime described by Araki et al. (2001). All animals were humanely killed. Statistical comparisons were made using Student’s t tests, or one-way ANOVA followed by post-hoc Bonferroni tests. All data are expressed as mean ± S.E.M. STN neurones in slices from MPTP-lesioned animals fire at 4.73 ± 0.42 Hz (n =54), significantly slower than those from control animals (9.78 ± 1.16, n =20; p<0.0001). STN neurones from MPTP lesioned animals fire irregularly, with an average coefficient of variation of inter-spike interval of 78.9% (n =28), significantly higher (p=0.0007) than that seen in neurons from control animals (25.8%, n =33). Firing in simultaneously recorded STN neurones is uncorrelated, both in slices from control animals (n =2) and those from MPTP-lesioned animals (n=16). In cells from control animals, 30μM dopamine increases firing rate by 334.1 ±67.34% without significant effect on the regularity of firing (n=15). In cells from MPTP-lesioned animals, dopamine increases firing rate by 681.4 ±150.9 %, and significantly reduces the coefficient of variation of inter-spike interval (78.9% to 26.2%, p<0.001, n =28). Application of CNQX (10μM) AP5 (100μM) and picrotoxin (50μM) cause no significant change in firing pattern or rate in neurons from MPTP-lesioned animals. In summary, STN neurones in slices from MPTP-lesioned mice fire asynchronously, and significantly more slowly and less regularly than those from control animals. This latter effect can be reversed by applied dopamine, as has been reported in STN neurons in vitro from 6-hydroxydopamine-lesioned rats (Zhu et al. 2002).