SummaryRecently, there has been some evidence suggesting that exposure to neuroexcitotoxic amino acids, culminating in excessive neuronal calcium influx, may cause nerve cell destruction in motor neuron disease (MND). We therefore hypothesized that central calcium channel blockade with nimodipine might slow-down progression of MND. Two patients with sporadic MND were treated in a double-blind placebo controlled cross-over study with oral nimodipine (120 mg/day) for 5 months. Disease progression was assessed by repeated computerized measurements of isometric force from 20 muscle groups, and calculation of global force score. Global force deterioration slopes during the 5-month periods of nimodipine or placebo therapy were highly linear and almost identical. Nimodipine therefore does not seem to be effective in changing the course of MND. The observed remarkable linearity of disease course also confirms that cross-over methodology and serial measurements of muscle force are constructive tools in the clinical evaluation of novel therapetic strategies for this devastating disease.