The AXOPROBE-1A multipurpose microelectrode amplifier contains two microelectrode amplifiers (ME1 and ME2). These amplifiers may be independently used for intracellular and extracellular voltage recording with simultaneous current passing, or differentially for recording with ion-sensitive electrodes. Many built-in features make the AXOPROBE-1A extremely convenient to use. To learn how to make the most of these features, we advise first-time users of the AXOPROBE-1A to read this manual thoroughly and to familiarize themselves with the instrument using resistor/capacitor models of their electrodes and cells. HEADSTAGES The AXOPROBE-1 A is designed to be used with the full range of microelectrode resistances, from hundreds of kO to tens of Gft. To accomodate this range, a variety of interchangeable headstages are available. These all record at unity voltage gain but have different current-passing gains (H). Headstages also come with a choice of capacitance neutralization ranges. The range depends on the size of the capacitor used for neutralization. The high-frequency noise is also proportional to this capacitor. Usually the headstages are supplied with the smallest capacitor (L version) but other choices are available. The actual current in each microelectrode is measured. That is, the measurement falls to zero if the microelectrode blocks even though a current command is set up. During current passing, up to ±30 V can be applied across the microelectrode to enable control of current in high-resistance electrodes. For ion-selective electrode measurements either one or both headstages can be ultrahigh input impedance types.