Spinal manipulative therapy techniques are commonly employed by physiotherapists in the clinical setting for the management of neuromusculoskeletal pain and dysfunction, although their underlying mechanism is not fully understood. Mulligan's sustained natural apophyseal glides (SNAGs) constitute one of these techniques. This preliminary investigation was undertaken to investigate the relationship between the application of cervical SNAGs to the C5/6 intervertebral joint (with cervical right rotation) and indirect measures of sympathetic nervous system (SNS) activity. Previous investigations have suggested that cervical manipulative therapy techniques, separate to cervical SNAGs, result in a sympatheoexcitatory effect and that this may be instrumental in producing an analgesic response. Sixteen asymptomatic subjects participated in a laboratory-based experiment. A single blind, randomized, within subject, repeated measures study design which included control, placebo and treatment comparisons was used. Measures of skin conductance (SC) and skin temperature (ST) in the right and left upper limbs were used as indicators of SNS activity. The cervical SNAG technique produced a sympathoexcitatory response demonstrated by a significant increase in SC during application of the treatment intervention (P<0.0005) and for a 2-min period after the intervention (P=0.001) compared with control. There was also a significant increase in SC for the placebo condition, both during intervention (P=0.015) and after intervention (P=0.011) compared with control. There was a statistically significant difference in SC between placebo and treatment conditions for the 2-min period after the intervention had been applied (P=0.01). A trend did emerge for ST change, illustrating a decrease in ST for the treatment and placebo conditions compared with control, however this did not reach statistically significant levels. There were no apparent left/right upper limb differences for SC and ST for each condition. The results of this study suggest that cervical SNAG techniques, performed on naïve asymptomatic subjects, have a sympathoexcitatory effect as measured by changes in SC and ST. The importance of this sympathoexcitatory effect in relation to potential mechanisms for manipulation induced analgesia are discussed, and further areas of research proposed.