For ease of use, ctypes is the way to go.
The following example of ctypes is from actual code I've written (in Python 2.5). This has been, by far, the easiest way I've found for doing what you ask.
import ctypes
# Load DLL into memory.
hllDll = ctypes.WinDLL ("c:\\PComm\\ehlapi32.dll")
# Set up prototype and parameters for the desired function call.
# HLLAPI
hllApiProto = ctypes.WINFUNCTYPE (
ctypes.c_int, # Return type.
ctypes.c_void_p, # Parameters 1 ...
ctypes.c_void_p,
ctypes.c_void_p,
ctypes.c_void_p) # ... thru 4.
hllApiParams = (1, "p1", 0), (1, "p2", 0), (1, "p3",0), (1, "p4",0),
# Actually map the call ("HLLAPI(...)") to a Python name.
hllApi = hllApiProto (("HLLAPI", hllDll), hllApiParams)
# This is how you can actually call the DLL function.
# Set up the variables and call the Python name with them.
p1 = ctypes.c_int (1)
p2 = ctypes.c_char_p (sessionVar)
p3 = ctypes.c_int (1)
p4 = ctypes.c_int (0)
hllApi (ctypes.byref (p1), p2, ctypes.byref (p3), ctypes.byref (p4))
The ctypes stuff has all the C-type data types (int, char, short, void*, and so on) and can pass by value or reference. It can also return specific data types although my example doesn't do that (the HLL API returns values by modifying a variable passed by reference).
In terms of the specific example shown above, IBM's EHLLAPI is a fairly consistent interface.
All calls pass four void pointers (EHLLAPI sends the return code back through the fourth parameter, a pointer to an int so, while I specify int as the return type, I can safely ignore it) as per IBM's documentation here. In other words, the C variant of the function would be:
int hllApi (void *p1, void *p2, void *p3, void *p4)
This makes for a single, simple ctypes function able to do anything the EHLLAPI library provides, but it's likely that other libraries will need a separate ctypes function set up per library function.
The return value from WINFUNCTYPE is a function prototype but you still have to set up more parameter information (over and above the types). Each tuple in hllApiParams has a parameter "direction" (1 = input, 2 = output and so on), a parameter name and a default value - see the ctypes doco for details
Once you have the prototype and parameter information, you can create a Python "callable" hllApi with which to call the function. You simply create the needed variable (p1 through p4 in my case) and call the function with them.