The aim of this study was to evaluate the time course of breathing pattern and respiratory mechanics in patients with amyotrophic lateral sclerosis (ALS). A study was conducted on 25 out of 38 eligible ALS patients. Neurological status, arterial blood gases (ABGs), spirometry, breathing pattern (minute ventilation (V'E), tidal volume (VT), respiratory frequency (fR), duty cycle (duration of inspiration/duration of total breathing cycle (tI/ttot)), respiratory drive (P0.1)), respiratory mechanics (oesophageal pressure (Ppl), dynamic compliance (CL,dyn), pressure time product (PTP) and index (PTI), work of breathing (WOB)), and respiratory muscle (RM) strength as assessed by maximal oesophageal pressure (Ppl,max) were evaluated at presentation (to) in all patients and after 6 months (t6) in 11 patients. At to, the mean values of the degree of neurological impairment were 60+/-20 and 103+/-30 as assessed by the Norris scale and Medical Research Council (MRC) score, respectively. From the time of the first neurological symptom, survival time ranged 7-50 months. Diurnal ABGs were normal. A mild restrictive pattern was observed, a forced vital capacity (FVC) <70% of predicted being present in 45% of patients, only FVC % pred (r=0.59; p<0.05), forced expiratory volume in one second (FEV1) % pred (r=0.53; p<0.05) and survival (r=0.64; p<0.05) showing a significant correlation with the Norris scale. A Ppl,max <30 cmH2O was associated with a significantly greater mortality, Ppl,max being correlated with survival (r=0.79, p<0.05). At t6, fR, fR/VT, P0.1/Ppl,max, were significantly increased in comparison to to, while FVC % pred, vital capacity (VC) % pred, FEV1 % pred, VT and Ppl,max were significantly reduced. These results suggest a progressive deterioration in breathing pattern and in respiratory muscle strength with progression of disease.